冻结步态患者脚桥核与全脑静息态功能连接比较

Comparison of functional connection between pedunculopontine nucleus and whole brain resting state in freezing of gait

目的探讨脚桥核(PPN)静息态脑功能连接改变在帕金森病伴冻结步态(PD-FOG)和原发性进行性冻结步态(PPFG)中步态发生机制的作用,并比较两者差异。方法研究组纳入PD-FOG 11例、PPFG 10例,25例匹配的不伴冻结步态的帕金森病(PD-NFOG)作为对照组。通过冻结步态问卷(FOGQ)、帕金森病统一评定量表第Ⅲ部分(UPDRSIII)、帕金森病统一评定量表第Ⅱ部分(UPDRSⅡ)、简易智能精神状态检查量表(MMSE)、汉密尔顿抑郁量表(HAMD)、HY分级量表评价被试者背景运动、认知及情绪背景。所有被试者在停用抗帕金森病(PD)药物12 h进行静息状态功能磁共振扫描。在全脑水平进行PPN和全脑静息态功能连接的分析,并比较PD-FOG组、PPFG组与PD-NFOG组PPN脑功能连接的差异。结果年龄、性别、病程、MMSE、HAMD、UPDRSII在3组间差异无统计学意义。PD-FOG和PD-NFOG患者UPDRSⅢ、HY分级差异无统计学意义。PD-FOG组和PPFG组患者FOGQ的差异无统计学意义。PD-FOG和PD-NFOG组UPDRSⅢ评分显著高于PPFG组。PPN全脑功能连接显示:与PD-NFOG比较,PD-FOG组右侧PPN(PPN-R)与岛叶及小脑连接减弱,梭状回及海马旁回连接增强;左侧PPN(PPN-L)与丘脑、岛叶连接减弱。与PD-NFOG比较,PPFG组PPN-R与颞叶连接减弱,与枕叶连接增强;PPN-L与颞叶连接减弱,与小脑及额叶连接增强。PPFG与PD-FOG比较, PPN-L与颞叶连接增强,与楔叶及枕叶连接减弱,两组PPN-R全脑功能连接差异无统计学意义。结论 PD-FOG与PPFG冻结步态均与PPN脑功能连接异常相关,但具体机制存在一定差异。PD-FOG与PPN-运动环路(小脑、丘脑)及感觉联络皮层(岛叶、颞叶)功能连接减弱、PPN-边缘系统(海马旁回、梭状回)连接增强有关。PPFG主要和PPN与感觉联络皮层(颞叶、枕叶、楔叶)连接减弱有关,但与PPN-运动环路(小脑、丘脑)功能连接受损关系不大。

Objective To evaluate the effect of pedunculopontine nucleus(PPN) in function connectivity in the mechanism of gait disorder in Parkinson’s disease(PD) with freezing of gait(PD-FOG) and primary progressive freezing of gait(PPFG), and to compare the differences between them. Methods 11 Parkinson’s disease patients with freezing of gait were collected, included 11 patients with Parkinson’s disease with freezing of gait(PD-FOG), 10 patients diagnosed as primary progressive freezing of gait(PPFG), and 25 matched PD patients without freezing of gait(PD-NFOG). All the subjects were evaluated by Freezing of Gait Questionnaire(FOGQ), Unified Parkinson’s Disease Rating Scale Ⅲ(UPDRSIII), Unified Parkinson’s Disease Rating Scale II(UPDRSII), Minimum Mental State Examination(MMSE), Hamilton Depression Scale(HAMD), Hoehn & Yahr Scale(HY) to find out movement, cognitive and emotional background. All subjects underwent a resting state functional MRI scan for 12 hours after taking medicine. Functional connectivity with pedunculopontine nucleus(PPN) was analyzed. Seed to cluster analysis was performed at whole brain level and compared among three groups. Results Age and gender, duration of disease, MMSE, and HAMD,UPDRSII were not significantly different among three groups. There was no significant difference in UPDRSⅢand HY staging between PD-FOG and PD-NFOG patients. There was no significant difference in FOGQ between the PD-FOG group and the PPFG group. The UPDRSⅢ scores of the PD-FOG and the PD group was significantly higher than those of the PPFG group. The fMRI of whole brain function connectivity showed that compared with PD-NFOG, the right side PPN(PPN-R) was weakened in connectivity with the in the insular and cerebellum, and the fusiform and ParaHippocampal connections were enhanced in PD-FOG group;In PD-FOG the left side PPN(PPN-L) weakened connection with the thalamus and insula. Compared with PD-NFOG, in PPFG group PPN-R was weakened in connection with temporal lobe and enhanced in connection with the occipital lobe;and PPN-L weakened in connection with temporal lobe and enhanced in connection with cerebellum and frontal lobe. Compared with PD-FOG, in PPFG group, PPN-L increased the connection with temporal lobe, and weakened the connection between wedge and occipital lobe, and there was no significant difference in the functional connectivity of PPN-R between PPFG group and PD-FOG group. Conclusion The freezing of gait of PD and PPFG are related to the abnormal connection of PPN brain function, but the mechanism is different. The freezing of gait of PD is related to the weakened functional connection between the PPN-motor circuit(cerebellum, thalamus) and the sensory cortex(island, temporal lobe) and the enhanced connection of the PPN-limbic system(ParaHippocampus, fusiform). The mechanism of PPFG is mainly related to the weakening of the connection between the PPN and the sensory cortex(the temporal lobe the occipital lobe and the cuneus), but it has little to do with the functional connection of the PPN-motor circuit(cerebellum and thalamus).